The role of a ciliary GTPase in the regulation of neuronal maturation of olfactory sensory neurons.

Olfactory sensory neurons (OSNs) form embryonically and mature perinatally, innervating glomeruli and extending dendrites with multiple cilia. This process and its timing are crucial for odor detection and perception and continues throughout life. In the olfactory epithelium (OE), differentiated OSNs proceed from an immature (iOSN) to a mature (mOSN) state through well-defined sequential morphological and molecular transitions, but the precise mechanisms controlling OSN maturation remain largely unknown. We have identified that a GTPase, ARL13B, has a transient and maturation state-dependent expression in OSNs marking the emergence of a primary cilium. Utilizing an iOSN-specific Arl13b-null murine model, we examined the role of ARL13B in the maturation of OSNs. The loss of Arl13b in iOSNs caused a profound dysregulation of the cellular homeostasis and development of the OE. Importantly, Arl13b null OSNs demonstrated a delay in the timing of their maturation. Finally, the loss of Arl13b resulted in severe deformation in the structure and innervation of glomeruli. Our findings demonstrate a previously unknown role of ARL13B in the maturation of OSNs and development of the OE.

Public funding for private for-profit centres and access to cataract surgery by patient socioeconomic status: an Ontario population-based study.

BACKGROUND: Public funding of cataract surgery provided in private, for-profit surgical centres increased to help mitigate surgical backlogs during the COVID-19 pandemic in Ontario, Canada. We sought to compare the socioeconomic status of patients who underwent cataract surgery in not-for-profit public hospitals with those who underwent this surgery in private for-profit surgical centres and to evaluate whether differences in access by socioeconomic status decreased after the infusion of public funding for private, for-profit centres. METHODS: We conducted a population-based study of all cataract operations in Ontario, Canada, between January 2017 and March 2022. We analyzed differences in socioeconomic status among patients who accessed surgery at not-for-profit public hospitals versus those who accessed it at private for-profit surgical centres before and during the period of expanded public funding for private for-profit centres. RESULTS: Overall, 935 729 cataract surgeries occurred during the study period. Within private for-profit surgical centres, the rate of cataract surgeries rose 22.0% during the funding change period for patients in the highest socioeconomic status quintile, whereas, for patients in the lowest socioeconomic status quintile, the rate fell 8.5%. In contrast, within public hospitals, the rate of surgery decreased similarly among patients of all quintiles of socioeconomic status. During the funding change period, 92 809 fewer cataract operations were performed than expected. This trend was associated with socioeconomic status, particularly within private for-profit surgical centres, where patients with the highest socioeconomic status were the only group to have an increase in cataract operations. INTERPRETATION: After increased public funding for private, for-profit surgical centres, patient socioeconomic status was associated with access to cataract surgery in these centres, but not in public hospitals. Addressing the factors underlying this incongruity is vital to ensure access to surgery and maintain public confidence in the cataract surgery system.

Characterizing the Impact of Procedure Funding on the Covid-19 Generated Procedure Gap in Ontario: A Population-Based Analysis.

BACKGROUND: Surgical procedures in Canada were historically funded through global hospital budgets. Activity-based funding models were developed to improve access, equity, timeliness, and value of care for priority areas. COVID-19 upended health priorities and resulted in unprecedented disruptions to surgical care, which created a significant procedure gap. We hypothesized that activity-based funding models influenced the magnitude and trajectory of this procedure gap. METHODS: Population-based analysis of procedure rates comparing the pandemic (March 1, 2020-December 31, 2021) to a prepandemic baseline (January 1, 2017-February 29, 2020) in Ontario, Canada. Poisson generalized estimating equation models were used to predict expected rates in the pandemic based on the prepandemic baseline. Analyses were stratified by procedure type (outpatient, inpatient), body region, and funding category (activity-based funding programs vs. global budget). RESULTS: In all, 281,328 fewer scheduled procedures were performed during the COVID-19 period compared with the prepandemic baseline (Rate Ratio 0.78; 95% CI 0.77-0.80). Inpatient procedures saw a larger reduction (24.8%) in volume compared with outpatient procedures (20.5%). An increase in the proportion of procedures funded through activity-based programs was seen during the pandemic (52%) relative to the prepandemic baseline (50%). Body systems funded predominantly through global hospital budgets (eg, gynecology, otologic surgery) saw the least months at or above baseline volumes, whereas those with multiple activity-based funding options (eg, musculoskeletal, abdominal) saw the most months at or above baseline volumes. CONCLUSIONS: Those needing procedures funded through global hospital budgets may have been disproportionately disadvantaged by pandemic-related health care disruptions.

Surgical Outcomes among Focused versus Diversified Cataract Surgeons.

PURPOSE: Narrowly focused surgical practice has become increasingly common in ophthalmology and may have an effect on surgical outcomes. Previous research evaluating the influence of surgical focus on cataract surgical outcomes has been lacking. This study aimed to evaluate whether surgeons' exclusive surgical focus on cataract surgery influences the risk of cataract surgical adverse events. DESIGN: Population-based cohort study. PARTICIPANTS: All patients 66 years of age or older undergoing cataract surgery in Ontario, Canada, between January 1, 2002, and December 31, 2013. METHODS: Outcomes of isolated cataract surgery performed by exclusive cataract surgeons (no other types of surgery performed), moderately diversified cataract surgeons (1%-50% noncataract procedures), and highly diversified cataract surgeons (>50% noncataract procedures) were evaluated using linked healthcare databases and controlling for patient-, surgeon-, and institution-level covariates. Surgeon-level covariates included both surgeon experience and surgical volume. MAIN OUTCOME MEASURES: Composite outcome incorporating 4 adverse events: posterior capsule rupture, dropped lens fragments, retinal detachment, and suspected endophthalmitis. RESULTS: The study included 1 101 864 cataract operations. Patients had a median age of 76 years, and 60.2% were female. Patients treated by the 3 groups of surgeons were similar at baseline. Adverse events occurred in 0.73%, 0.78%, and 2.31% of cases performed by exclusive cataract surgeons, moderately diversified surgeons, and highly diversified surgeons, respectively. The risk of cataract surgical adverse events for patients operated on by moderately diversified surgeons was not different than for patients operated on by exclusive cataract surgeons (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.00-1.18). Patients operated on by highly diversified surgeons had a higher risk of adverse events than patients operated on by exclusive cataract surgeons (OR, 1.52; 95% CI, 1.09-2.14). This resulted in an absolute risk difference of 0.016 (95% CI, 0.012-0.020) and a number needed to harm of 64 (95% CI, 50-87). CONCLUSIONS: Exclusive surgical focus did not affect the safety of cataract surgery when compared with moderate levels of surgical diversification. The risk of cataract surgical adverse events was higher among surgeons whose practice was dedicated mainly to noncataract surgery.

Effect of variations of corneal physiology on novel non-invasive intraocular pressure monitoring soft contact lens.

Glaucoma is the leading cause of irreversible blindness around the world. With its slow asymptomatic progression, there is an emphasis on early detection and frequent monitoring. A novel microfluidic contact lens has been established as a potential way to track the fluctuations of the intraocular pressure (IOP) which is a key indicator for diagnosing and monitoring glaucoma progression. The purpose of this article is to determine the effect of physiological variations of the eye on the performance of the microfluidic contact lens. Ultrasound biomicroscopy (UBM) was used to measure the central corneal thickness (CCT) and radius of corneal curvature (RCC) for a series of 16 fresh enucleated porcine eyes. The effect of these corneal anatomic features on device performance was then assessed by systematically adjusting intraocular pressure from 10 to 34 mmHg and monitoring the device indicator response. The performance of the microfluidic contact lens was determined by finding the amount the indicator fluid shifted in position as a result of 1 mmHg IOP increase. The relationship between IOP and indicator fluid was found to be linear for all eyes. The slope of the indicator fluid movement as a result of the IOP was evaluated against the CCT and RCC of each porcine eye. This yielded low correlation coefficients, 0.057 for CCT and 0.024 for RCC, meaning that these physiological differences showed no systematic impact on the measurements made with the contact lens.

Evolution in the Risk of Cataract Surgical Complications among Patients Exposed to Tamsulosin: A Population-Based Study.

PURPOSE: Tamsulosin is associated with intraoperative floppy iris syndrome (IFIS), an important risk factor for complications during cataract surgery. Significant efforts have been made to increase awareness of the risks associated with tamsulosin, and educational initiatives have fostered the uptake of technical adjustments to decrease adverse event rates among tamsulosin-exposed patients. However, the effectiveness of these efforts at the population level has not been studied. DESIGN: Population-based study to evaluate cataract surgical adverse event rates over time among patients exposed to tamsulosin and those not exposed to this drug. PARTICIPANTS: All male patients 66 years of age and older undergoing cataract surgery in Ontario, Canada, between January 1, 2003, and December 31, 2013, were included in the study. METHODS: Linked healthcare databases were used to study the evolution in the risk of cataract surgical adverse events over time among tamsulosin-exposed and non-tamsulosin-exposed patients adjusting for patient-, surgeon-, and institution-level covariates. The study timeframe incorporated periods before and after the first reports of tamsulosin-associated IFIS. MAIN OUTCOME MEASURES: Four important cataract surgical adverse events were evaluated: posterior capsule rupture, dropped lens fragments, retinal detachment, and suspected endophthalmitis. RESULTS: Among patients exposed to tamsulosin, the risk of surgical adverse events decreased over time (odds ratio, 0.95 per year; 95% confidence interval, 0.91-0.99 per year). This trend was observed across patient age strata. Among patients not recently exposed to tamsulosin, the risk of surgical adverse events also decreased over time (odds ratio, 0.96 per year; 95% confidence interval, 0.95-0.98 per year). CONCLUSIONS: The risk of cataract surgical complications among both tamsulosin-exposed and non-tamsulosin-exposed patients declined between 2003 and 2013. Tamsulosin remains an important risk factor for cataract surgical adverse events, and ongoing efforts will be needed to develop and disseminate surgical approaches that mitigate the risks posed by tamsulosin.

Cataract Surgery Quality and Capacity.

Cataract surgery is the most common operation performed in most developed countries, including Canada. Nuanced, evidence-driven policies are needed to ensure appropriate access to this sight-saving operation while maintaining the highest standards in quality of care. The Vision Health Services Research Program at Queen's University, in partnership with members of the Ontario Provincial Vision Task Force, has developed evidence to inform policies aimed at optimizing both access and quality across the eye care spectrum.

New Surgeon Outcomes and the Effectiveness of Surgical Training: A Population-Based Cohort Study.

PURPOSE: Reports have questioned the technical proficiency of newly graduating surgeons. However, objective data supporting these concerns are limited. Surgical outcomes among recent graduates are an important indicator of residency programs' ability to graduate surgeons who are ready to meet the needs of their patients. This study aimed to investigate the association between a surgeon's number of years of independent practice and the risk of surgical adverse events. DESIGN: Population-based cohort study. PARTICIPANTS: All patients 66 years of age or older undergoing isolated cataract operations in Ontario, Canada, between January 1, 1997, and December 31, 2013. METHODS: Cataract surgical outcomes for all operations performed by surgeons commencing practice in the study period were evaluated using linked health care databases. MAIN OUTCOME MEASURES: Four serious complications were evaluated: posterior capsule rupture, dropped lens fragments, retinal detachment, and suspected endophthalmitis. Analyses controlled for patient-, surgeon-, and institution-level covariates. RESULTS: The study evaluated 1 431 320 cataract operations. Surgeons in their first year of independent practice were more than 9 times more likely to have high complication rates (≥2%) than surgeons in their tenth year (odds ratio [OR], 9.3; 95% confidence interval [CI], 2.7-31.9). Each additional year of independent practice was associated with a 10% decrease in the risk of patients experiencing an adverse surgical event (OR, 0.90 per year of surgeon independent practice; 95% CI, 0.87-0.94). CONCLUSIONS: In this population-based study, surgical complications were significantly more likely early in surgeons' careers. Interventions may be needed in postgraduate surgical training and early independent career monitoring and mentoring processes to ensure patient safety while continually renewing the surgical workforce.

Effect of cataract surgery volume constraints on recently graduated ophthalmologists: a population-based cohort study.

BACKGROUND: Across Canada, graduates from several medical and surgical specialties have recently had difficulty securing practice opportunities, especially in specialties dependent on limited resources such as ophthalmology. We aimed to investigate whether resource constraints in the health care system have a greater impact on the volume of cataract surgery performed by recent graduates than on established physicians. METHODS: We used population-based administrative data from Ontario for the period Jan. 1, 1994, to June 30, 2013, to compare health services provided by recent graduates and established ophthalmologists. The primary outcome was volume of cataract surgery, a resource-intensive service for which volume is controlled by the province. RESULTS: When cataract surgery volume in Ontario entered a period of government-mandated zero growth in 2007, the mean number of cataract operations performed by recent graduates dropped significantly (-46.37 operations/quarter, 95% confidence interval [CI] -62.73 to -30.00 operations/quarter), whereas the mean rate for established ophthalmologists remained stable (+5.89 operations/quarter, 95% CI 95% CI -1.47 to +13.24 operations/quarter). Decreases in service provision among recent graduates did not occur for services without volume control. The proportion of recent graduates providing exclusively cataract surgery increased over the study period, and recent graduates in this group were 5.24 times (95% CI 2.15 to 12.76 times) more likely to fall within the lowest quartile for cataract surgical volume during the period of zero growth in provincial cataract volume (2007-2013) than in the preceding period (1996-2006). INTERPRETATION: Recent ophthalmology graduates performed many fewer cataract surgery procedures after volume controls were implemented in Ontario. Integrated initiatives involving multiple stakeholders are needed to address the issues facing recently graduated physicians in Canada.

Anti-inflammatory therapy after selective laser trabeculoplasty: a randomized, double-masked, placebo-controlled clinical trial.

PURPOSE: To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes. DESIGN: Randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Patients with primary open-angle or pseudo-exfoliation glaucoma. METHODS: Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT. MAIN OUTCOME MEASURES: Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit. RESULTS: Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups (P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point (P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance (P > 0.15 for analyses at all time points). Treatment failure rates were not different among groups (P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups. CONCLUSIONS: Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.

Unintended consequences of delisting routine eye exams on retinopathy screening for people with diabetes in Ontario, Canada.

BACKGROUND: Routine eye examinations for healthy adults aged 20-64 years were delisted from the Ontario Health Insurance Plan in 2004, but they continue to be insured for people with diabetes regardless of age. We sought to assess whether the delisting of routine eye examinations for healthy adults had the unintended consequence of decreasing retinopathy screening for adults with diabetes. METHODS: We used administrative data to calculate eye examinations for people with diabetes ages 40-64 years and 65 years and older in each 2-year period from 1998 to 2010. We examined differences by sex, income, rurality and type of health care provider. We used segmented linear regression to assess the change in trend before and after 2004. RESULTS: For people with diabetes aged 65 years and older, eye examinations rose gradually from 1998 to 2010, with no substantial change between 2004 and 2006. For people with diabetes aged 40-65 years, there was an 8.7% (95% confidence interval [CI] 6.3%-11.1%) decrease in eye examinations between 2004 and 2006. Results were similar for all population subgroups. Ophthalmologic examinations decreased steadily for both age groups during the study period, and there was a decline in optometry examinations for people ages 40-65 years after 2004. INTERPRETATION: The delisting of routine eye examinations for healthy adults in Ontario had the unintended consequence of reducing publicly funded retinopathy screening for people with diabetes. More research is needed to understand whether patients are being charged for an insured service or to what degree misunderstanding has prevented patients from seeking care.

Systemic effects of intravitreal vascular endothelial growth factor inhibitors.

PURPOSE OF REVIEW: The development of vascular endothelial growth factor (VEGF) inhibitors has revolutionized the treatment of retinal diseases. However, VEGF functions in many physiological and pathological processes. Consequently, inhibition of this signalling molecule carries the potential to cause serious adverse events. RECENT FINDINGS: Numerous clinical trials, meta-analyses and population-based studies have provided data regarding the safety of intravitreal VEGF inhibitor injections. Although individual trials and some meta-analyses have not found significant risks, other meta-analyses have suggested possible risks, especially in patients with multiple baseline risk factors. Population-based studies have not found increased risks of vascular adverse events. SUMMARY: Overall, results across studies with differing methodologies provide some reassurance that the widespread use of intravitreal injections of VEGF inhibitors has not resulted in significant increases in the risks of adverse events. However, ongoing vigilance and further study remain priorities, with a particular need for greater evaluation of high-risk subgroups. Rapidly evolving treatment options for ocular diseases including new drugs and new delivery technologies will require ongoing evaluations of safety.

Correlation between corneal and contact lens deformation with changes in intraocular pressure for wearable monitoring systems.

OBJECTIVE: The aim of this work is to evaluate the extent to which the eye's curvature deformation, due to changes in the intraocular pressure (IOP), can be directly tracked by an overlying contact lens. METHOD: In this experimental study, using 12 cadaveric eyes, the IOP was increased from 10 to 36 mmHg, while video imaging was used to capture the three experimental variations. The deformation of the bare eye was used as a control, while the deformation of an overlying silicone grided contact lens and an overlying microfluidic IOP-sensing contact lens were examined and compared. RESULTS: The relation between the slope of the radius of corneal curvature versus the IOP for both the bare eye and the marker contact lens yielded a linear relationship with a R2 value of 0.83. The microfluidic contact lens resulted in an average performance of 0.40 mm indicator movement/mmHg (SD 0.006). Comparing the slope of the marker contact lens deformation, to the performance of the microfluidic contact lens resulted in a R2 value of 0.78. The strain map of the overlaying grided contact lens showed most deformation occurring along the outer edge of the lens with increased deformation as increase IOP occurs; as well as with some negative, compressive movement near the central points. CONCLUSION: The deformation from the curvature of the eye is significant enough from 10 to 36 mmHg that a silicone contact lens can capture and mimic those changes. The results show promise for optimization in contact lens-based IOP monitoring.

Association of topical glaucoma medications with lacrimal drainage obstruction and eyelid malposition.

BACKGROUND/OBJECTIVES: Adverse effects of topical glaucoma medications (TGMs) may include development of ocular adnexal disorders. We undertook a study to determine the effect of TGMs on the risk of developing lacrimal drainage obstruction (LDO) and eyelid malposition. SUBJECTS/METHODS: All patients 66 years of age and older in Ontario, Canada initiating TGM and all patients diagnosed with glaucoma/suspected glaucoma but not receiving TGM from 2002 to 2018 were eligible for inclusion in this retrospective cohort study. Using validated healthcare administrative databases, cohorts were identified with TGM and no TGM patients matched 1:2 on sex and birth year. The effect of TGM treatment on risk of surgery for LDO and lid malpositions was estimated using Kaplan-Meier and Cox proportional hazards models. RESULTS: Cohorts included 122,582 patients in the TGM cohort and 232,336 patients in the no TGM cohort. Among the TGM cohort there was decreased event-free survival for entropion (log-rank P < 0.001), trichiasis (P < 0.001), and LDO (P = 0.006), and increased ectropion-free survival (P = 0.007). No difference in ptosis-free survival was detected (P = 0.78). For the TGM cohort there were increased hazards for entropion (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.12-1.37; P < 0.001), trichiasis (HR 1.74, 95% CI 1.57-1.94; P < 0.001), and LDO (at 15 years: HR 2.39, 95% CI 1.49-3.85; P = 0.004), and a decreased hazard for ectropion (HR 0.89, 95% CI 0.81-0.97; P = 0.008). No association between TGM treatment and ptosis hazard was detected (HR 0.99, 95% CI 0.89-1.09; P = 0.78). CONCLUSIONS: TGMs are associated with an increased risk of undergoing surgery for LDO, entropion, and trichiasis.

Expanding the scope of an eConsult service: acceptability and feasibility of an optometry-ophthalmology pilot project.

OBJECTIVE: To determine the feasibility and acceptability of connecting optometrists to ophthalmologists on an eConsult service. DESIGN: Descriptive analysis of utilization data and an anonymous survey. PARTICIPANTS: All eConsult cases sent by optometrists between March 2019 and February 2020 (utilization data); optometrists and ophthalmologists participating in the eConsult Vision Pilot Project (survey). METHODS: Utilization data for the study period were collected automatically and underwent descriptive analysis. Participating optometrists and ophthalmologists received an email invitation to a survey assessing the project. RESULTS: Thirteen optometrists from 5 clinics in the southeast region and 7 ophthalmologists were recruited to participate in the pilot project. Optometrists sent 109 eConsults in a 13-month period, representing 33% of all cases submitted to ophthalmology through the eConsult service provincially (March 2019-March 2020). Sixty-eight percent of respondents to an anonymous online survey valued the recruitment and engagement of eye care professionals from the same health region. The influence of the eConsult service was reported to have a "somewhat positive" (27%) to "very positive" (50%) influence on the relationship between the two professional groups. CONCLUSION: The eConsult Vision Pilot Project fills a gap in service and provides an opportunity for patients to get access to specialty advice. We demonstrated that allowing optometrists to solicit specialist advice from ophthalmologists was acceptable and feasible.

Ontario Cataract Quality Outcome Initiative: appropriateness and prioritization of cataract surgery.

OBJECTIVE: To explore the utility of the Catquest 9SF visual function (VF) questionnaire along with visual acuity (VA) for determining appropriateness and priority for cataract surgery. To evaluate the feasibility of administering the Catquest-9SF in a clinical setting using web-based electronic data capture and interpretation. DESIGN: Prospective multicentred interventional observational study. PARTICIPANTS: Subjects undergoing sequential cataract surgery in both eyes at 4 sites in Ontario. METHODS: We recorded best-corrected VA (BCVA) and VA with current correction (CCVA) in each eye and both eyes (OU) and Catquest-9SF responses on a tablet before and after cataract surgery. Linear regression models were employed to test for associations between VA and visual function (VF). RESULTS: Preoperative BCVA and CCVA in the worse eye were significant predictors of change in VF (p = 0.006 and p = 0.008, respectively); subjects with worse VA had a greater improvement in VF after surgery. There was a significant association between improvement in VF and improvement in CCVA OU (p = 0.001). Fourteen of 151 subjects (9%) had no improvement or worse VF scores after surgery. Within this group, 10 of 14 subjects had a preoperative score ≤-3, which is suggestive of minimal visual disability. Within this subset, 4 of 14 subjects (2.6%) had a preoperative BCVA of 20/30 or better in their worse eye. CONCLUSIONS: For patient groups with equal VA, the Catquest-9SF score can help determine priority for surgery. Web-based data capture and interpretation allow for efficient virtual assessments of VF. A BCVA in the worse eye of 20/30 or better combined with a Catquest-9SF score <-3 can be used as a guideline for lowest priority.

Stroke rates after introduction of vascular endothelial growth factor inhibitors for macular degeneration: a time series analysis.

OBJECTIVE: To assess whether stroke rates among patients with retinal disease were influenced by the rapid and sequential uptakes of bevacizumab and ranibizumab for age-related macular degeneration (AMD). DESIGN: Population-based, time series analysis using encrypted, linked healthcare databases in Ontario, Canada. PARTICIPANTS: We included all patients aged 66 years or older with physician-diagnosed retinal disease in the previous 5 years between 2002 and 2010 (N = 116 388). A secondary analysis evaluated patients who had undergone photodynamic therapy (PDT) within the preceding year (N = 10 059). METHODS: We used segmented regression analysis to evaluate changes in the rate of hospitalization for ischemic stroke associated with the introduction of bevacizumab and ranibizumab. The stroke rate was compared across 3 mutually exclusive periods: the period before the availability of bevacizumab or ranibizumab, the period of bevacizumab dominant AMD therapy, and the period of ranibizumab dominant AMD therapy. MAIN OUTCOME MEASURES: Hospitalizations for ischemic stroke. RESULTS: Among patients with retinal disease, neither the trend nor the level of the stroke time series changed with the uptake of bevacizumab (trend change coefficient -0.0026 stroke hospitalizations/1000 subjects/month [95% confidence interval {CI}, -0.0066 to 0.0014; P = 0.20]; level change coefficient, 0.036 stroke hospitalizations/1000 subjects [95% CI, -0.070 to 0.14; P = 0.51]), or ranibizumab (trend change coefficient: -0.0011 stroke hospitalizations/1000 subjects/month [95% CI, -0.0087 to 0.0065; P = 0.78]; level change coefficient: -0.017 stroke hospitalizations/1000 subjects [95% CI, -0.14 to 0.11; P = 0.79]). Similar results were observed in the analysis restricted to patients with recent PDT and in analyses stratified on age, sex, history of stroke, and history of diabetes. CONCLUSIONS: The rapid uptake of vascular endothelial growth factor (VEGF) inhibitors for AMD was not associated with a change in the rate of hospitalization for stroke among Ontario seniors with retinal disease. Furthermore, stroke rates in the bevacizumab and ranibizumab periods were not different. These population-level results complement the findings of a recently published trial comparing bevacizumab and ranibizumab, and may assist clinicians and policy makers as they balance the comparative efficacy, safety, and cost of these 2 closely related treatments.